Evidence map›Paper›PMID 41708903›Full record

ArticleDrug delivery and translational research2026

Comparative analysis of clinically approved lipid nanoparticles for intranasal siRNA delivery against SARS-CoV-2.

Yuan Zhang, Matt D Johansen, Scott Ledger, Rebecca Shipley, Guanshu Zhao, Ernest Moles, Stuart Turville, Pall Thordarson, Philip M Hansbro, Maria Kavallaris and 2 more

Abstract read
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In one paragraph

Article in Drug delivery and translational research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Yuan ZhangKirby Institute, UNSW, Sydney, NSW, 2052, Australia.
Matt D JohansenCentre for Inflammation, Faculty of Science, School of Life Sciences, Centenary Institute and University of Technology Sydney, Sydney, NSW, 2050, Australia.
Scott LedgerKirby Institute, UNSW, Sydney, NSW, 2052, Australia.
Rebecca ShipleyCentre for Inflammation, Faculty of Science, School of Life Sciences, Centenary Institute and University of Technology Sydney, Sydney, NSW, 2050, Australia.
Guanshu ZhaoCentre for Inflammation, Faculty of Science, School of Life Sciences, Centenary Institute and University of Technology Sydney, Sydney, NSW, 2050, Australia.
Ernest MolesUNSW RNA Institute, UNSW Sydney, Sydney, 2052, Australia.
Stuart TurvilleKirby Institute, UNSW, Sydney, NSW, 2052, Australia.
Pall ThordarsonUNSW RNA Institute, UNSW Sydney, Sydney, 2052, Australia.
Philip M HansbroCentre for Inflammation, Faculty of Science, School of Life Sciences, Centenary Institute and University of Technology Sydney, Sydney, NSW, 2050, Australia.
Maria KavallarisUNSW RNA Institute, UNSW Sydney, Sydney, 2052, Australia.
Anthony D KelleherKirby Institute, UNSW, Sydney, NSW, 2052, Australia.
Chantelle L AhlenstielKirby Institute, UNSW, Sydney, NSW, 2052, Australia. cahlenstiel@kirby.unsw.edu.au.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

SARS-CoV-2 continues to circulate globally, with persistent hospitalizations, despite a successful global vaccination strategy. We have developed highly conserved, antiviral short interfering (si)RNA and demonstrated in vivo antiviral efficacy following intranasal treatment of mice with naked siRNA. To enhance antiviral efficacy and siRNA protection, in this study we investigated the use of LNP packaging to improve delivery and efficacy. We examined three clinically approved lipid nanoparticle (LNP) formulations that mimic the compositions of Alnylam's Onpattro (MC3), Moderna's Spikevax (SM-102), and Pfizer-BioNTech's Comirnaty (ALC-0315) RNA-based therapeutics, to identify the optimal formulation for antiviral siRNA therapeutic respiratory delivery and antiviral efficacy. All LNP formulations assessed showed successful delivery of siRNA to respiratory cells in vitro and provided effective silencing of siRNA targeted SARS-CoV-2 genes. However, the MC3-based LNP-siRNA (MC3 LNP-siRNA) treatment elicited the least off-target immune activation, with no induction of interferon stimulated genes. Additionally, the MC3 LNP-siRNA remained effective when administered 24 h post-infection, significantly reducing viral RNA levels in vitro. Chemical modification of siRNA with 2'‑O‑methyl incorporation further attenuated immune activation, without compromising efficacy. In vivo intranasal delivery of MC3 LNP-siRNA was generally well tolerated, with no adverse effects on body weight or pulmonary function at therapeutic doses, although mild pulmonary leukocyte infiltration was observed at higher or repeated doses. Our study demonstrates that LNP-encapsulated and chemically modified siRNAs can provide an effective and mutation-resilient antiviral strategy. This study compares clinically relevant LNP formulations for siRNA delivery to the respiratory tract, demonstrating that MC3-based LNPs offer a promising platform for safe and effective RNA therapeutic delivery.

Indexed as

Drug deliveryLipid nanoparticlesRNA interferenceSARS-CoV-2SiRNA

Identifiers

PMID41708903

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.